Studies on the increased activity of cross-linked dimers of bovine pancreatic ribonuclease toward double-stranded RNA's are being extended to examination of spermine-RNase combinations. The products are being tested toward poly A times poly U and the hybrid poly rU times poly dA. Since ribonuclease dimers are about ten times as effective as the monomer in inhibiting the growth of tumor cells, the spermine-RNase derivatives will be tested for cytotoxicity against proliferating cells. The research will include consideration of the components of the cell by which the derivatives of ribonuclease may be more strongly bound than the monomer. Cross-linked combinations of ribonuclease and deoxyribonuclease are also being prepared for study of their action on hybrid substrates. The observation that the human placenta contains isolatable amounts of an inhibitor of ribonuclease is leading to detailed characterization of the inhibitor from this tissue. Its binding properties for sterols and for derivatives of ribonuclease are under study. Research on the possible function of the inhibitor includes measurement of its concentration during development of the placenta in the rat, the sub-cellular distribution of the protein, and the possibility of the preparation of derivatives of ribonuclease which would be less strongly bound by the inhibitor for test of their embryotoxicity.